What is the usage and dosage of Prothiaden (dosulepin) for treating depression and anxiety?

Prothiaden (Dosulepin) for Depression and Anxiety

Prothiaden (dosulepin/dothiepin) is an effective tricyclic antidepressant for treating depression and anxiety, with a typical dosage of 75-150 mg daily given as a single nighttime dose, demonstrating comparable efficacy to other tricyclics but with a notably better tolerability profile, particularly regarding anticholinergic side effects. 1

Primary Indications

Dosulepin is indicated for treating: 2

• Psychoneurotic patients with depression and/or anxiety 2
• Depression and/or anxiety associated with alcoholism (contraindicated with concurrent alcohol use) 2
• Depression and/or anxiety associated with organic disease 2
• Psychotic depressive disorders with associated anxiety, including involutional depression and manic-depressive disorders 2

Target symptoms that respond particularly well include anxiety, tension, depression, somatic symptoms, sleep disturbances, guilt, lack of energy, fear, apprehension, and worry. 2

Dosing Recommendations

Standard Dosing

• Initial dose: 75 mg daily as a single nighttime dose 3, 1
• Therapeutic range: 75-225 mg/day 4
• Most common maintenance dose: 75-150 mg/day (75% of patients require 125-150 mg/day) 4
• Maximum studied dose: 150 mg as a single nightly dose 1

Special Populations

• Elderly patients: Start with 50-75 mg as a single nighttime dose 3
• Pediatric patients: Not recommended for children under 12 years of age due to lack of clinical experience 2

Efficacy Profile

Comparative Effectiveness

Dosulepin demonstrates therapeutic equivalence to other established tricyclic antidepressants: 5

• Similar overall efficacy to amitriptyline 5
• Comparable to imipramine, doxepin, maprotiline, mianserin, fluoxetine, fluvoxamine, and trazodone 5
• Statistically superior response compared to sustained-release amitriptyline (Lentizol) at weeks 1,2, and 4 of treatment 3

Treatment Duration

• 75% of patients achieve remission and discontinue therapy by 9 months 4
• Approximately 20% of patients require long-term therapy exceeding 2 years, particularly those with chronic depressive states in inadequate personalities 4
• Safe for long-term use, with documented treatment periods exceeding 2 years 4

Tolerability and Safety

Adverse Effect Profile

Dosulepin has a superior tolerability profile compared to other tricyclics, particularly amitriptyline: 3, 1

• Most common side effect: Dry mouth (reported in approximately 2.5% of patients requiring withdrawal) 4
• Drowsiness (reported in approximately 1.7% requiring withdrawal) 4
• Overall withdrawal rate due to side effects: 9.7% 4
• Significantly less drowsiness, weight gain, and increased appetite compared to doxepin 1
• Lower incidence of anticholinergic side effects compared to amitriptyline 5

Cardiovascular Safety

Dosulepin has not been associated with cardiotoxicity at therapeutic doses: 5

• Minor ECG changes may occur (observed in 2 of 25 patients in one study) but are not associated with clinical cardiovascular deterioration 3
• No consistent clinically significant changes in pulse or blood pressure 3
• However, as with all tricyclics, obtain screening ECG for patients over 40 years and use caution in patients with ischemic cardiac disease or ventricular conduction abnormalities 6

Clinical Considerations and Pitfalls

Sedative Properties

• Dosulepin has sedative/anxiolytic activity similar to amitriptyline, making it particularly useful for patients with coexisting anxiety and sleep disturbances 5
• Single nighttime dosing capitalizes on sedative effects to improve sleep while minimizing daytime drowsiness 3, 1

Special Clinical Situations

Depression in psychotic disorders: 7

• Dosulepin is effective and well-tolerated when combined with neuroleptics for treating depression during psychosis evolution 7
• In a study of 124 patients with chronic psychosis and depression, 95% received concomitant neuroleptic treatment with significant improvement (HDRS score decreased from 23.78 to 8.48 over 45 days) 7
• Withdrawal rate due to side effects was only 6.5% in this population 7

Contraindications and Cautions

• Do not use concomitantly with alcohol in patients with alcoholism-related depression 2
• Consider drug interactions when treating depression associated with organic disease in patients receiving other medications 2
• As with all TCAs, limit dosages to less than 100 mg/day when possible in high-risk cardiac patients 6
• Allow 6-8 weeks for adequate trial, including at least 2 weeks at the highest tolerated dosage 6